An Efficient Partial Reduction of α,β‐Unsaturated Esters Using DIBAL‐H in Flow

Abstract

The partial reduction of α,β‐unsaturated esters and benzoate derivatives to form the corresponding aldehydes was achieved using a flow reactor system within 1 s at a high flow rate (18 mL min–1) under cryogenic conditions (–97 °C). Commercially available diisobutylaluminium hydride (DIBAL‐H) was used as the reductant. The desired enals and benzaldehyde derivatives, except for 4‐methoxycinnamate and 4‐methoxybenzoate, were formed selectively and redox economically in moderate to high yields.

Design, synthesis and biological evaluation of GPR55 agonists

“…Alternatively, this reaction was also examined using flow chemistry. It was previously determined that aryl esters were especially difficult to reduce to the aldehyde, 24–25 but using high flow rates (50 mL/min), cold temperatures (−78 °C), and short reaction times (0.037 sec), we were able to obtain a moderate yield of the aldehyde ( 14 ) directly, although with some over-reduction to the alcohol ( 13 ). For simplicity, it was decided to fully convert ester 12 to alcohol 13 and then oxidize it to the aldehyde.…”

“…Following related reports, 24–25 solutions of methyl 6-bromo-2-naphthoate in toluene ( 12 ; 0.1 M) and DIBAL-H in toluene (0.3 M) were added via inhouse built syringe pumps 43 into 0.04 inch internal diameter tubing at a rate of 25 mL/min. Each solution was precooled to −78 °C before mixing by submerging 1.6 feet of steel tubing into a dry ice/acetone bath.…”

Synthesis and Property of Unsymmetric Bent-core Liquid Crystals Based on 2,5-Disubstitueted-1,3,4-oxadiazole

“…缓慢滴加 SOCl 2 (100 mL), 控制温度不 超过 0 ℃; 滴毕, 自然升至室温, 再加热回流 8 h. 停止 加热, 冷至室温; 将反应混合液倒入冰水(200 mL)中充 分搅拌; 萃取分液, 用乙酸乙酯(100 mL×3)提取有机 层; 合并有机层, 用 10%的 Na 2 CO 3 溶液洗至中性. 蒸干 溶剂, 油泵减压蒸馏, 得 95.5 g 无色透明液体 4 [13] , 产率 92.2%. b.p.…”

Study for diastereoselective aldol reaction in flow: synthesis of (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid, a key component of cyclodepsipeptide HDAC inhibitors

“…For instance, we recently succeeded in improving the synthesis of enal 9 by a partial reduction of a, b-unsaturated esters 8 using commercially available diisobutylaluminium hydride (DIBAL-H) in flow, providing some hundreds of milligrams of enal 9. 12 The desired b-hydroxy acid derivative 5 can be produced by basic hydrolysis of 10, followed by removal of the resulting chiral auxiliary by simple filtration. Therefore, we subsequently aimed to establish an integrated flow system for synthesizing the a, b-unsaturated ester 8 and the aldol 10 as a step toward reliably producing sufficient quantities of 5.…”

“…A partial reduction of the a, b-unsaturated ester 8 to the enal 9 in flow We next performed a partial reduction of 8 to give the enal 9 once the flow synthesis of a, b-unsaturated ester 8 had been achieved. 12 The flow system we used to achieve this partial reduction is shown in Fig. 4.…”